Theoretical origin of life: chaperones required (Introduction)

by David Turell , Monday, May 31, 2021, 15:36 (1061 days ago) @ David Turell

All protein processes in life make mistakes. Chaperones had to exist at the origin of life:

https://www.pnas.org/content/118/21/e2020885118.long

"Across the Tree of Life, life’s phenotypic diversity has been accompanied by a massive expansion of the protein universe. Compared with simple prokaryotes that harbor thousands of proteins, plants and animals harbor hundreds of thousands of proteins that are also longer, multidomain, and comprise a variety of folds and fold combinations, repeated segments, and beta-rich architectures that make them prone to misfolding and aggregation. Surprisingly, the relative representation of core chaperones, those dedicated to maintaining the folding quality of these increasingly complex proteomes, did not change from prokaryotic to mammalian genomes. To reconcile the expanding proteomes, core chaperones have rather increased in cellular abundance and evolved to function cooperatively as a network, combined with their supporting workforce, the cochaperones.

"Abstract
Across the Tree of Life (ToL), the complexity of proteomes varies widely. Our systematic analysis depicts that from the simplest archaea to mammals, the total number of proteins per proteome expanded ∼200-fold. Individual proteins also became larger, and multidomain proteins expanded ∼50-fold. Apart from duplication and divergence of existing proteins, completely new proteins were born. Along the ToL, the number of different folds expanded ∼5-fold and fold combinations ∼20-fold. Proteins prone to misfolding and aggregation, such as repeat and beta-rich proteins, proliferated ∼600-fold and, accordingly, proteins predicted as aggregation-prone became 6-fold more frequent in mammalian compared with bacterial proteomes. To control the quality of these expanding proteomes, core chaperones, ranging from heat shock proteins 20 (HSP20s) that prevent aggregation to HSP60, HSP70, HSP90, and HSP100 acting as adenosine triphosphate (ATP)-fueled unfolding and refolding machines, also evolved. However, these core chaperones were already available in prokaryotes, and they comprise ∼0.3% of all genes from archaea to mammals. This challenge—roughly the same number of core chaperones supporting a massive expansion of proteomes—was met by 1) elevation of messenger RNA (mRNA) and protein abundances of the ancient generalist core chaperones in the cell, and 2) continuous emergence of new substrate-binding and nucleotide-exchange factor cochaperones that function cooperatively with core chaperones as a network.

"All cellular life is thought to have stemmed from the last universal common ancestor (LUCA), that emerged more than 3.6 billion y ago. Two major kingdoms of life diverged from LUCA: bacteria and archaea, which about 2 billion y later merged into the eukaryotes. Since the beginning of biological evolution, life’s volume has increased on a grand scale: The average size of individual cells has increased ∼100-fold from prokaryotes to eukaryotes, the number of cell types has increased ∼200-fold from unicellular eukaryotes to humans, and average body size has increased ∼5,000-fold from the simplest sponges to blue whales.

"This expansion in organismal complexity and variability was accompanied by an expansion in life’s molecular workforce, proteomes in particular, which in turn presented a challenge of reaching and maintaining properly folded and functional proteomes. Most proteins must fold to their native structure in order to function, and their folding is largely imprinted in their primary amino acid sequence. However, many proteins, and especially large multidomain polypeptides, or certain protein types such as all-beta or repeat proteins, tend to misfold and aggregate into inactive species that may also be toxic. Life met this challenge by evolving molecular chaperones that can minimize protein misfolding and aggregation, even under stressful out-of-equilibrium conditions favoring aggregation. Chaperones can be broadly divided into core and cochaperones. Core chaperones can function on their own, and include ATPases heat shock protein 60 (HSP60), HSP70, HSP100, and HSP90 and the adenosine triphosphate (ATP)-independent HSP20. The basal protein holding, unfolding, and refolding activities of the core chaperones are facilitated and modulated by a range of cochaperones such as J-domain proteins. (my bold)

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"Thus, across the Tree of Life, proteomes have massively expanded, not just by duplication of preexisting proteins but also by the emergence of completely new ones. Eukaryotic proteomes became particularly large and specifically richer in repeat, beta-rich, and aggregation-prone proteins whose folding is inherently challenging. These changes in proteome size and composition intensified the demand for chaperone action. Curiously, however, no new core chaperones emerged in response to this increased demand. Instead, they increased in abundance relative to all other proteins in the cell. Foremost, an entire network of cochaperones had evolved that facilitate the basal core-chaperone activity."

Comment: The design of the origin of life required correcting chaperones and cochaperones from the very beginning. Without arguing about a designer, the design creation had to have had knowledge aforehand of the impending problem a life based on proteins must have. Therefore a mechanism of chaperoning and cochaperoning exists. Natural events do not have foresight. A designer is reqired.